Pharmacogenomics research and clinical implementation in Brazil

Abstract

We searched PubMed entries and the Lattes database of Brazilian Pharmacogenetics Network investigators, for pharmacogenetic/genomic (PGx) studies in the Brazilian population, focusing on the drugs and genes included in the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Warfarin was the most extensively studied drug in a PGx context: a genomewide association study targeting warfarin stable dose identified significant signals in VKORC1 and CYP2C9, several PGx dosing algorithms were developed based on these and other genes, and the implications of population admixture on extrapolation of dosing recommendations in the CPIC guidelines were examined. A study in renal transplanted patients disclosed association of CYP3A5*6 and CYP3A5*7 with tacrolimus dosing, which led to addition of these variants to CYP3A5*3 in the CPIC tacrolimus guideline. Studies verified predisposition of HIV-positive carriers of UGT1A1*28 to severe atazanavir-induced hyperbilirubinaemia, intolerance to 5-fluorouracyl in gastrointestinal cancer patients with deleterious DPYD variants, failure of HCV-infected carriers of IFNL3 rs12979860 to obtain a sustained viral response to PEG-IFN-α, and hypersensitivity reactions to abacavir in HIV-positive carriers of HLA-B*57:01. No prospective analyses of drug therapy outcomes or cost-effectiveness assessments of PGx-guided therapy were found. In conclusion, the limited adoption of PGx-informed drug prescription in Brazil reflects combination of recognized barriers to PGx implementation worldwide plus factors specific to the Brazilian population. The latter include rarity/absence of genetic variants on which international PGx guidelines are based (eg HLA-B*15.02 for phenytoin and carbamazepine) and the caveat of extrapolating to the admixed Brazilian population, guidelines based on categorical variables, such as continental ancestry (eg warfarin guidelines), "race" or ethnicity.

Nurse empowerment through Pharmacogenetics

“…The clinical implementation of pharmacogenetics is a challenge worldwide and has been very well accepted in cases where: 1) the evidence of the genetic association is reproducible and consistent, and 2) the clinical consequences of the presence of a certain allele are serious, for example, slow metabolizers using drugs with a narrow therapeutic window ( 8 , 11 ) . For the implementation, tests are required for each local population, and most of the scientific evidence is from Caucasian and North American populations.…”

“…In addition, the area of oncology is intensively incorporating the study of the genetic bases of cancer and, consequently, specific pharmacological approaches for patients with certain risk alleles ( 17 ) . The challenge of implementing pharmacogenetics in clinical practice has several obstacles ( 8 , 11 ) , which have been faced in a multidisciplinary way. There are several notes in the literature about the need for nurses to actively participate in this process, both to contribute to the consolidation of the tool itself and to enable its application to their daily lives ( 3 , 15 - 17 , 21 - 22 ) .…”

“…From the point of view of public health management, nurses have a crucial role in assessing the cost-benefit of applying this approach in professional practice. In fact, the urgent need to conduct this type of research in Brazil is clear ( 8 , 11 ) . In the present study, we tried to envision the role that the public university can play in promoting the beginning of the application of pharmacogenomics in the single health system by offering these tests at cost.…”

“…In the data collection stage, it allows the health team to detect the individual’s genetic data, outlining a diagnosis that will guide care planning ( 12 ) . Thus, in the same way that it is necessary to obtain local information to adapt concepts of pharmacogenetics to our population that has a mixed ethnic origin ( 8 , 11 ) , it is necessary to understand whether and how this knowledge can be applied to the nurse’s daily life.…”

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

“…Some reports have established the need to analyze the clinical implication of pharmacogenetics from the genotypic, haplotype and phenotypic perspective and not only focus on one level of information, since genomic variants can vary throughout the different populations and their effect on the phenotype of interest can be modified by one or more variants [48]. For Latin American populations, including Colombia, it is common to see mixed populations with different percentages of ancestries (Table 5) and it is recognized that it is a continuous rather than a categorical variable, even within the self-reported race / color categories [49].…”